Research Snapshot: UF researchers use 3D models to evaluate immunotherapy treatment in glioblastoma and osteosarcoma

By Bayli DiVita Dean, Ph.D.

University of Florida Health Cancer Center researchers have developed a promising new method to evaluate how a type of immunotherapy treatment called CAR T-cell therapy kills tumor cells.

A new tool developed by UF researchers helps evaluate immunotherapy treatment by providing a way to visualize the tumor microenvironment to understand how CAR T-cells interact with tumor cells.

CAR T-cells represent a promising arm of cancer immunotherapy. The cells, isolated from cancer patients, are armed to target a particular protein that is highly expressed in the tumor and subsequently kill the tumor cells. In the context of CAR-T therapy, animal models offer some advantages, but they often require using immune-deficient mice to allow for tumor engraftment and prevent CAR T-cells from being rejected.

In the new study, published recently in the journal Acta Biomaterialia, the researchers developed a novel model to better mimic tumor and CAR-T cell interactions. The In Vitro ImmunoTherapy Assays, or iVITA, mimic the extracellular matrix, which is the complex network of molecules outside of the cell, by using a microgel platform.

Using iVITA, the researchers found CD70 CAR T-cells were able to infiltrate tumors at higher levels when CAR T-cells were cultured with CD70+-expressing glioblastoma or osteosarcoma tumor cells than when they were cultured with control tumor cells. 

“This iVITA technology is a very important tool to evaluate immunotherapy,” said Jianping Huang, M.D., Ph.D., a co-author on the new study and an associate professor in the department of neurosurgery who leads clinical laboratory operations at the Preston A. Wells Jr. Center for Brain Tumor Therapy. “It allows us to visualize the most important components of the tumor microenvironment and know how CAR T-cells interact with the tumor cells.”

“We hope to ultimately use this technology by placing some of the patient’s tumor in the iVITA system and treating it with CAR T-cells to better predict which patients will respond to CAR T therapy,” said Paul Castillo Caro, M.D., a co-author and assistant professor in the department of pediatrics. Castillo Caro is a physician-scientist at the T cell Engineering Laboratory of the Pediatric Cancer Immunotherapy Initiative at the University of Florida.

Castillo Caro and Huang are members of the UF Health Cancer Center, which receives crucial support for its research from the Casey DeSantis Cancer Research Act (Fla. Stat. § 381.915). The study was also funded by the National Science Foundation Graduate Research Fellowship, Merck & Co., the National Institutes of Health, the Bankhead Coley Research Program, the Florida Department of Health Live Like Bella Pediatric Cancer Research Initiative, UF’s Clinical & Translational Science Institute and the Department of Defense Cancer Research Program.

To learn more about the Wells Brain Tumor Center at the University of Florida, visit its website.

Read the article in Acta Biomaterialia.

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